Studies were performed to determine if patients with sickle cell disease (SCD), with pneumococcal sepsis or meningitis were capable of producing opsonizing activity to their infecting strain of S. pneumoniae during hospitalizaiion, in comparison to children without SCD. Six patients without SCD and one patient with SCD were studied. The older children without SCD responded to their infecting strains of S. pneumoniae with the development of opsonizing activity more efficiently than the younger cildren. The child with SCD did not develop any opsonizing activity to her infecting strain during the two week period of hospitalization. Polymorphonuclear leukocyte bactericidal activity for S. aureus 502A and a type 10 test strain of S. pneumoniae were also measured during infection in four of the six control children. In two of the children, leukocyte bactericidal activity for S. aureus 502A was decreased during the 9th to 12th days post admission, but not prior to or after this time. In the other two children, leukocyte bactericidal activity for both bacterial strains was normal. Levels and activities of the classical and alternative complement pathways were also measured on the six control children and the child with SCD, and were found to be normal. Leukocyte bactericidal activity for S. aureus 502A and the type 10 S. pneumoniae, and serum opsonic activity for the type 10 S. pneumoniae were also measured on seven patients with SCD during vaso-occlusive crisis. All of the patients had normal leukocyte bactericidal activity for both bacterial strains. In addition, no change in opsonic activity was observed during crisis in comparison to opsonic activity when the patients were asymptomatic.